Risk of stroke/systemic embolism, major bleeding, and associated costs in non-valvular atrial fibrillation patients who initiated apixaban, dabigatran, or rivaroxaban compared with warfarin in the United States medicare population: updated analysis

Abstract

Objective

To provide an updated comparison of the risk and cost of stroke/systemic embolism (SE) and major bleeding between direct oral anticoagulants (DOAC: apixaban, rivaroxaban, dabigatran) and warfarin among non-valvular atrial fibrillation (NVAF) patients.

Methods

Adults (≥65 years) initiating warfarin or DOACs between 1 January 2013 and 31 December 2014 were selected from the Medicare database and propensity scores matched 1:1 to balance baseline characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major bleeding-related medical costs in each matched cohort.

Results

Of the 264,479 eligible patients, 38,740 apixaban-warfarin pairs, 76,677 rivaroxaban-warfarin pairs, and 20,955 dabigatran-warfarin pairs were matched. Apixaban (Hazard Ratio [HR] = 0.46; 95% Confidence Interval [CI] 0.38–0.56) and rivaroxaban (HR = 0.71; 95% CI 0.63–0.80) were associated with a significantly lower risk of stroke/SE compared to warfarin. Apixaban (HR = 0.57; 95% CI 0.51–0.63) and dabigatran (HR = 0.80; 95% CI 0.70–0.90) were associated with a significantly lower risk of major bleeding; rivaroxaban (HR = 1.14; 95% CI 1.07–1.21) was associated with a significantly higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban and rivaroxaban had significantly lower stroke/SE-related medical costs; and apixaban and dabigatran had significantly lower major bleeding-related medical costs.

Conclusions

This real-world analysis showed DOACs to be associated with a lower risk of stroke/SE and major bleeding, and lower medical costs compared to warfarin. Among them, only apixaban appears to be associated with a significantly lower risk of all three outcomes collectively: stroke/SE, major bleeding, and lower related medical costs compared to warfarin.

Keywords:

• Warfarin
• stroke
• direct oral anticoagulants
• atrial fibrillation
• cost

Transparency

Declaration of funding

This work was funded by Pfizer Inc. and Bristol-Myers Squibb.

Declaration of financial/other relationships

Amin reported serving as PI or co-I of clinical trials sponsored by NIH/NIAID, NeuroRx Pharma, Pulmotect, Blade Therapeutics, Novartis, Takeda, Humanigen, Eli Lilly, PTC Therapeutics, OctaPharma, Fulcrum Therapeutics, Alexion, unrelated to the present study; speaker and/or consultant for BMS, Pfizer, BI, Portola, Sunovion, Mylan, Salix, Alexion, AstraZeneca, Novartis, Nabriva, Paratek, Bayer, Tetraphase, Achogen LaJolla, Ferring, Seres, Millenium, Spero, Eli Lilly, PeraHealth, HeartRite, Aseptiscope, Sprightly, unrelated to the present study. Keshishian, Zhang is an employee of STATinMED Research, a paid consultant to Pfizer and Bristol-Myers Squibb in connection with this study and the development of this manuscript. Hines, Dina, and Liu are employees of Pfizer Inc., with ownership of stocks in Pfizer Inc. Le, Rosenblatt, and Vo are employees of Bristol-Myers Squibb Company. Rosenblatt and Vo have ownership of stocks in Bristol-Myers Squibb Company. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

Michael Moriarty provided medical writing and editorial support with STATinMED Research which is a paid consultant to Bristol-Myers Squibb and Pfizer. Statistical programming for this study was provided by Yingchu Zhao and Yiyun Lin of STATinMED Research which is a paid consultant to Bristol-Myers Squibb and Pfizer. Onur Baser of STATinMED Research, a paid consultant to Bristol-Myers Squibb and Pfizer, and Columbia University contributed to the design and methodology of this study.